PROJECT SUMMARY Psychotic disorders including schizophrenia [SZ] and bipolar disorder [BD] are among the most costly and debilitating psychiatric diseases worldwide. Both SZ and BD are associated with marked cognitive deficits, which are among the strongest predictors of poor community functioning, disability, and reduced quality of life (1-3). Cognitive remediation (CR) is one of the few available interventions to target cognitive symptoms directly. Growing evidence indicates that CR improves cognition in patients with these illnesses at the group level (e.g. 4-6). However, a number of critical knowledge gaps limit our ability to develop robust, individualized CR interventions and provide access to patients who are most likely to benefit: first, CR outcomes are highly heterogeneous and predictors of treatment response have not been identified; and second, the underlying neurobiological mechanisms that mediate cognitive and functional enhancement remain largely undetermined. CR trials are challenging, as interventions are often lengthy and intensive, and ascertainment and retention of patients with psychotic disorders is difficult. As a result, the majority of CR studies are underpowered to clearly identify predictors of response, compare treatment effects by diagnosis, examine the ability of CR to drive rapid neural change, and determine the extent to which neural change is associated with cognitive or functional outcomes. These knowledge gaps have limited our ability to develop robust, targeted CR programs and deliver them to patients most likely to benefit. The aims of this project are twofold: 1) identification of patient characteristics associated with cognitive treatment response including baseline demographic, clinical, and cognitive variables, and multivariate models; and 2) examination of CR's ability to drive rapid, EEG-measured neural change in key information processing systems, and the associations of this change with primary cognitive outcomes. Over the last eight years our group has completed two separate randomized controlled trials of a 70-hour CR program in patients with SZ and BD with funding from NIMH and the Brain and Behavior Research Foundation. These studies employed identical CR paradigms, active control conditions, primary (cognitive) and secondary (clinical, functional) outcome measures taken at the same timepoints (baseline, midpoint, and post-treatment), and EEG protocols. We will systematically examine moderator of CR response across the sample including demographic, clinical and cognitive variables; we will then use principal components analysis (PCA) with regression to evaluate factors predictive of CR response, compare univariate predictors with our multivariate models, and explore clustering behavior in responders vs. non-responders. Finally, we will examine early effects of CR training on EEG-measured neurophysiology, and the relationship of neural modulation to cognitive response. This project is uniquely positioned to fill critical gaps in the knowledge by merging two related datasets to form a well- powered study able to answer these questions across affective and non-affective psychosis.